title: Local expression of interleukin-27 ameliorates collagen-induced arthritis.
abstract: OBJECTIVE
  To determine the mechanism of action of interleukin-27 (IL-27) against rheumatoid arthritis (RA).
  
  
  METHODS
  Adenovirus containing IL-27 transcript was constructed and was locally delivered into the ankles of mice with collagen-induced arthritis (CIA). Progression of arthritis was determined in treated and untreated mice by measuring ankle circumference and through histologic analysis. IL-17 and its downstream targets as well as cytokines promoting Th17 cell differentiation were quantified by enzyme-linked immunosorbent assay in CIA mouse ankles locally expressing adenoviral IL-27 as well as in control-treated mouse ankles. Ankles from both treatment groups were immunostained for neutrophil and monocyte migration (macrophages in the tissue). Finally, vascularization was quantified by histology and by determining ankle hemoglobin levels.
  
  
  RESULTS
  Ectopic expression of IL-27 in CIA mice ameliorated inflammation, lining hypertrophy, and bone erosion as compared with control-treated CIA mice. Serum and joint levels of IL-17 were significantly reduced in the IL-27-treated group compared with the control-treated group. Two of the main cytokines that induce Th17 cell differentiation and IL-17 downstream target molecules were greatly down-regulated in CIA mouse ankles receiving forced expression of IL-27. The control mice had higher levels of vascularization and monocyte trafficking than did mice ectopically expressing IL-27.
  
  
  CONCLUSIONS
  Our results suggest that increased levels of IL-27 relieve arthritis in CIA mouse ankles. This amelioration of arthritis involves a reduction in CIA mouse serum and joint levels of IL-17 and results in decreased IL-17-mediated monocyte recruitment and angiogenesis. Hence, the use of IL-27 may be a strategy for treatment of patients with RA.
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Pickens
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Chamberlain
authors.forename: Michael V
authors.initials: MV
authors.lastname: Volin
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mandelin
authors.forename: Hemant
authors.initials: H
authors.lastname: Agrawal
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsui
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahrara
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000843:Ankle Joint / Q000378:metabolism* / Q000473:pathology; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D020381:Interleukin-17 / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D014162:Transfection
chemical_list: D020381:Interleukin-17